title: Effects of endothelin-1 chronic stimulation on electrical restitution, beat-to-beat variability of repolarization, and ventricular arrhythmogenesis.
abstract: Chronically elevated levels of endothelin-1 (ET-1) have been detected in several cardiovascular diseases. In this study, we investigated the chronic effects of ET-1 on the electrophysiological characteristics expected to influence the genesis and maintenance of ventricular arrhythmia (VA). Rabbits were randomized to ET-1 (ET-1 group) or 0.9% saline (control group) for 2 weeks. The S1-S2 protocol and S1-S1 dynamic pacing were performed to assess the action potential duration restitution (APDR) and to induce APD alternans or VA in 4 sites of Langendorff-perfused rabbit hearts. The beat-to-beat variability of repolarization was quantified as short-term variability and long-term variability. Compared with the control group, chronic ET-1 administration significantly prolonged QT intervals, APD at 90% repolarization (APD₉₀), and effective refractory period (ERP), steepened the maximum slopes of the APDR curve, decreased the ERP/APD₉₀ ratio, and increased the spatial dispersions of APD₉₀, ERP, and maximum slopes (P < 0.05 for all). Moreover, chronic ET-1 administration markedly increased the short-term variability and long-term variability (P < 0.01 for all). APD alternans occurred in both groups, but the threshold of APD alternans was decreased at all sites in the ET-1 group (P < 0.01 for all). We also observed that chronic ET-1 stimulation significantly increased the incidence and duration of the VA episodes. These results suggest that chronic stimulation with ET-1 facilitated VA by steepening the APDR curve and increasing the spatial dispersion of APDR and beat-to-beat variability of repolarization.
authors.affiliation: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; †Cardiovascular Research Institute, Wuhan University, Wuhan, China; ‡Department of Cardiology, The First Clinical Medical College of Three Gorges University, Yichang, China; and §Department of Emergency, Central Hospital of Wuhan, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Mu
authors.initials: M
authors.lastname: Qin
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Shi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D054715:Cardiotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D010477:Perfusion; D011817:Rabbits; D011897:Random Allocation; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D054715:Cardiotoxins; D019332:Endothelin-1